National Foundation for Infectious Diseases

This CME activity has been planned and produced in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME), and is made possible by an unrestricted educational grant to the National Foundation for Infectious Diseases from sanofi pasteur.

Issued: July 2005

REDUCING THE IMPACT OF MENINGOCOCCAL DISEASE IN ADOLESCENTS AND YOUNG ADULTS

FACULTYWilliam Schaffner, MD, ChairmanLee H. Harrison, MDSheldon L. Kaplan, MDElizabeth Miller, MDWalter A. Orenstein, MDGeorges Peter, MDNancy E. Rosenstein, MD

A CME offering from the

National Foundation for Infectious Diseases

Release Date: July 2005

Expiration Date: July 2007

Estimated Time to Complete Activity: 1.5 hours

William Schaffner, MD, Chairman Professor and Chair, Department of Preventive Medicine Professor of Medicine (Infectious Diseases) Vanderbilt University School of Medicine Nashville, Tennessee

Lee H. Harrison, MD Professor of Medicine Infectious Diseases Epidemiology Research Unit University of Pittsburgh School of Medicine Pittsburgh, Pennsylvania

Sheldon L. Kaplan, MD Professor and Vice Chairman for Clinical Affairs Department of Pediatrics Baylor College of Medicine Houston, Texas

Elizabeth Miller, MD Head of the Immunisation Department Communicable Disease Surveillance Centre Health Protection Agency Centre for Infections London, England

Walter A. Orenstein, MD Director, Vaccine Policy and Development Associate Director, Emory Vaccine Center Emory University School of Medicine Atlanta, Georgia

Georges Peter, MD Professor, Department of Pediatrics Brown Medical School Founding Director, Division of Pediatric Infectious Diseases Rhode Island Hospital Providence, Rhode Island

Nancy E. Rosenstein, MD Chief, Meningitis and Special Pathogens Branch Division of Bacterial and Mycotic Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta, Georgia

FACULTY

Copyright © 2005 by National Foundation for Infectious Diseases. All Rights Reserved.

REDUCING THE IMPACT OF MENINGOCOCCAL DISEASE IN ADOLESCENTS AND YOUNG ADULTS

Continuing Medical Education Information 1

Introduction 3

Epidemiology of Meningococcal Disease 5

Transmission and Pathogenesis: Examining Risk Factors 7

U.S. Immunization Recommendations 8

Presentations, Progression and Sequelae 11

Conclusion 15

References 16

Self-Assessment Examination 18

CME Evaluation 19

1

Target AudiencePrimary care physicians, pediatricians, infectious

disease specialists, college health professionals and

public health officials responsible for or interested in

communicable diseases.

Statement of NeedMeningococcal disease causes substantial morbidity and

mortality. Cyclical trends in disease epidemiology suggest

that persons across many age groups may be at increased

risk of disease and severe complications, including death.

U.S. immunization policy and recommendations changed

following approval of a conjugate meningococcal vaccine

for use in persons aged 11 to 55 years. All physicians and

public health officials interested in communicable

diseases should be aware of the new recommendations by

the Centers for Disease Control and Prevention’s Advisory

Committee on Immunization Practices and the scientific

data that provide rationale for an immunization strategy

designed to lessen the burden of meningococcal disease.

Educational FormatThis activity was developed by the faculty based on a

literature review and personal knowledge and expertise

about meningococcal disease.

Evaluation and ExamA course evaluation form and self-assessment examination

at the end of this monograph will provide participants

with the opportunity to critique the program content and

method of delivery, identify future educational needs and

possible bias in the presentation materials and complete

the self-assessment examination to receive CME credits.

AccreditationThis activity has been planned and implemented in

accordance with the Essential Areas and Policies of the

Accreditation Council for Continuing Medical Education

(ACCME) by the National Foundation for Infectious

Diseases (NFID). NFID is accredited by the ACCME to

provide Continuing Medical Education (CME) for

physicians. NFID takes responsibility for the content,

quality and scientific integrity of the CME activity.

NFID designates this CME activity for a maximum of 1.5

credits toward the AMA Physician’s Recognition Award of

the American Medical Association. Each physician should

claim only those hours of credit that he/she actually spent

on the educational activity.

CONTINUING MEDICAL EDUCATION INFORMATION

OBJECTIVES

After completing the monograph, physicians will be able to:

• Discuss the epidemiology of meningococcal

disease in terms of age, serogroup and

geographic distribution;

• Describe clinical presentations of

meningococcal disease;

• Outline U.S. immunization recommendations;

• Compare features of conjugate and

polysaccharide vaccines.

2

CONTINUING MEDICAL EDUCATION INFORMATION

Commercial SupportThis CME activity is made possible by an unrestricted

educational grant from sanofi pasteur to the National

Foundation for Infectious Diseases.

Financial DisclosuresLee H. Harrison, MD, has a financial interest/relationship

with sanofi pasteur in the form of research support,

consulting, and speaking fees.

Sheldon L. Kaplan, MD, has a financial interest/relationship

with sanofi pasteur in the form of a research grant, stipend

and/or fellowship.

Elizabeth Miller, MD, has a financial interest/relationship

with Chiron, Wyeth Pharmaceuticals and Baxter in the

form of provision of meningococcal surveillance reports

for submission to licensing authorities.

Walter A. Orenstein, MD, has no significant financial interests

or relationships to disclose in relation to this program.

Georges Peter, MD, has no significant financial interests or

relationships to disclose in relation to this program.

Nancy E. Rosenstein, MD, has no significant financial interests

or relationships to disclose in relation to this program.

William Schaffner, MD, has no significant financial interests

or relationships to disclose in relation to this program.

DisclaimerAny procedures, medications or other courses of diagnosis

or treatment discussed or suggested in this activity should

not be used by clinicians without evaluation of their

patient’s condition, possible contraindications or dangers

in use, review of any applicable manufacturer’s product

information and comparison with recommendations of

other authorities.

Release date: July 2005

Expiration date: July 2007

© National Foundation for Infectious Diseases, 4733 Bethesda Avenue, Suite 750, Bethesda, Maryland, 20814

INTRODUCTION

Following approval of the first conjugate vaccine

against meningococcal disease, the Centers for Disease

Control and Prevention’s (CDC) Advisory Committee

on Immunization Practices (ACIP) has broadened its

meningococcal disease vaccination recommendations.1

The ACIP recommends routine vaccination of young

adolescents with the meningococcal conjugate vaccine at

the pre-adolescent health care visit (11-12 years of age).

For those persons who have not previously received the

meningococcal conjugate vaccine, ACIP recommends

vaccination before high-school entry (approximately 15

years of age). Routine vaccination is also recommended for

college freshmen living in dormitories. By 2008, the goal

will be routine vaccination of all adolescents beginning

at 11 years of age.

This document describes meningococcal disease

epidemiology and disease burden among children,

adolescents and young adults in the U.S. It also discusses

prevention strategies for meningococcal disease, with a

focus on recommended use of the quadrivalent conjugate

meningococcal vaccine. An overview of the meningococcal

conjugate vaccination program in the United Kingdom,

implemented in 1999, provides an example of the benefits

of widespread conjugate immunization across a population.

Meningococcal disease is a potentially life-threatening

infection caused by the bacterium Neisseria meningitidis.

It affects 1,400 to 2,800 persons in the U.S. annually.1

Most cases are sporadic; less than 5% occur in outbreaks.2,3

Incidence is highest in children less than 2 years of age,

but approximately 50% of cases occur in those over 15

years. Temporal and geographic peaks have been noted,

however, in various age groups. A study in Maryland found

that in the 1990s, 30% of cases occurred in adolescents

and young adults.4 During the same period (1991 to

2002), 13% to 14% of disease countrywide was in persons

11 to 18 years of age (CDC. Unpublished data).2 The

annual disease rate generally ranges from 0.9 to 1.5

cases per 100,000, but clearly the overall and age-specific

incidence rates are markedly cyclical.

Meningococcal disease is associated with an overall case

fatality rate of 10% to 14%.1 Fatality rates can vary widely,

however, depending on prevalence of the disease, the nature

of the infection and societal conditions.5 Case fatality rates

generally increase with age,6 but again, aberrations have

been noted. During a decade-long span ending in 2002,

CDC surveillance reported fatality rates of 12% in those

aged 10 to 17 years and 14% in those aged 14 to 24 years

(CDC. Unpublished data).2 Beyond mortality, meningococcal

disease is also associated with substantial long-term

morbidity. Of those who survive, 11% to 19% have

permanent sequelae, such as hearing loss, brain damage,

renal failure or limb amputation.1,7,8

3

Meningococcal Disease Immunization Recommendations

In addition to the ACIP, other important groups have issued recommendations regarding meningococcal disease vaccination. These may be reviewed at the

following Web addresses: Advisory Committee on Immunization Practices www.cdc.gov/mmwr/PDF/rr/rr5407.pdf American Academy of Family Physicians www.aafp.org/x34406.xml American Academy of Pediatrics www.cispimmunize.org/pro/pdf/aapmengpolicy.pdf American College Health Association www.acha.org/projects_programs/men.cfm

INTRODUCTION

Five clinically relevant meningococcal serogroups, A,

B, C, Y and W-135, are responsible for nearly all disease

worldwide. Currently, serogroups B, C and Y cause the

majority of U.S. infections; serogroup A is extremely rare

in the U.S. and W-135 causes a very small proportion of

infections. However, serogroup distribution has changed

over time. Serogroup Y caused only 2% of U.S. cases in

the early 1990s but 39% of cases from 1996 to 2001 (this

specific change appears to be confined to the U.S. thus

far). Serogroup distribution also varies by age.3 Serogroup

B is the most common serogroup in infants, serogroup

C is most common in adolescents and young adults and

serogroup Y causes the majority of cases in those aged

65 years and older.2 Similar fluctuations in serogroups are

seen worldwide.

A quadrivalent conjugate meningococcal vaccine

(MCV4), approved for use in persons aged 11 to 55 years

(Menactra®, sanofi pasteur), is a key addition to existing

meningococcal disease prevention measures.1 Like the

polysaccharide vaccine, which has been licensed in the

United States since 1978, the quadrivalent conjugate offers

protection against four serogroups of N. meningitidis

(A, C, Y, W-135), the bacteria that cause meningococcal

disease. Successful conjugate vaccine technology, however,

offers additional benefits compared with polysaccharide

vaccines, including improved duration of protection,

induction of immunologic memory, booster responses and

reduction in nasopharyngeal bacterial carriage.

Routine vaccination is also recommended for groups that

have elevated risk. These groups include microbiologists

who are routinely exposed to isolates of N. meningitidis;

persons who travel to or reside in countries in which

N. meningitidis is epidemic; military recruits; and those

with complement deficiency or functional or anatomic

asplenia. In addition to these groups, all other adolescents

and college students who wish to reduce their risk of

meningococcal disease may elect to be vaccinated.

Widespread conjugate meningococcal vaccination should

decrease the risk of meningococcal disease in adolescents

and adults. Expectations for conjugate vaccines are based

on recent experience. In the U.K., widespread use of

conjugate meningococcal C vaccines has led to sharp

decreases in meningococcal C disease (which was respon-

sible for 30% to 40% of cases in the U.K.), reduction in

bacterial carriage and consequent reduction in incidence

in unimmunized persons.9,10 In the U.S., universal use

of conjugate Haemophilus influenzae type b (Hib) and

pneumococcal vaccines has led to sharp decreases in

meningitis cases caused by these bacteria.11,12 Because

of these immunization successes, meningococcal disease

is now the most common cause of bacterial meningitis

among children over 2 years of age, adolescents and young

adults in the U.S.11

4

Several factors make meningococcal

disease a matter of public health importance.

First, it is a communicable disease

associated with notable morbidity and

mortality. Second, isolated meningococcal

cases and outbreaks often cause serious

medical and social stress in communities and

are associated with increased costs — both

economic and social. Finally, each case of

meningococcal disease requires a public

health response (i.e., identification of close

contacts for prophylaxis).

5

N. MENINGITIDIS is a commensal bacterium of the human

nasopharynx that infrequently causes invasive disease.

Up to 10% to 30% of adolescents and young adults13-15

and 19% to 39% of adult males (military recruits)15 are

asymptomatic, transient nasopharyngeal carriers of N.

meningitidis, although most carry nonpathogenic strains.

Asymptomatic carriage rates in young children are much

lower (< 2%).14,15 Some carriers develop protective

antibodies against the organism.16 In a minority of

exposed individuals, N. meningitidis penetrates the

nasopharyngeal mucosa, reaches the bloodstream and

causes systemic disease.17

The rate of meningococcal disease in the U.S. generally

varied between 0.9 and 1.5 cases per 100,000 persons

for 4 decades. Although meningococcal disease occurs

throughout the year, incidence peaks in late winter and

early spring.11 Rates of meningococcal disease are highest

in infancy with a second spike in incidence in adolescence,

with a peak at around 18 years of age (Figure 1).2,6

The distribution of serogroups causing meningococcal

disease (A, B, C, Y, W-135) varies over time and by

geographic location.2 From 1988 through 1991, most U.S.

cases of meningococcal disease were caused by serogroups

B and C, with serogroup Y accounting for only 2% of

cases.3 More recently (1996 through 2001), serogroup Y

disease caused the largest proportion of cases (39%),

followed by serogroup C (31%) and serogroup B (23%).2

Although serogroup W-135 is relatively uncommon in the

U.S. and was not previously known to cause outbreaks, it

played a major role in an outbreak during the Hajj pilgrimage

to Mecca in 2000. Four cases of W-135 meningococcal

disease were identified in pilgrims returning to the U.S.

from Saudi Arabia and their close contacts.18

Serogroup A was a common cause of U.S. epidemics early

in the last century, but has been rare since World War II.

Serogroups A and C continue to predominate throughout

Asia and Africa,19 with serogroup A remaining the major

cause of meningococcal disease in sub-Saharan Africa

(the “meningitis belt”).20,21 Even so, serogroup W-135 was

responsible for a large meningitis outbreak in Burkina

Faso in 2002.22 The diversity in geographic distribution of

meningococcal serogroups causing disease, while

unexplained, is important given the ease and frequency

of travel and potential exposure to serogroups other than

those common to one’s region of residence.

Overall, serogroups B, C and Y cause a substantial propor-

tion of disease across all ages, but specific distribution

varies by age group.3 Recent U.S. data (2002) show that

infants and toddlers experience a higher proportion of

serogroup B disease than older age groups (Figure 2).2

Among young adults (18 to 34 years old), serogroup C is

the most common (48% of cases) and in those 65 years

and older, serogroup Y is most common (62%). In a

EPIDEMIOLOGY OF MENINGOCOCCAL DISEASE

Figure 1:Invasive Meningococcal Disease by Age and Sex in the U.S., 1992-1996

Rates of meningococcal disease were adjusted for race.Source: Rosenstein6

2

3

4

5

0-4

5-9

10-1

4

15-1

9

20-2

4

25-2

9

30-3

4

35-3

9

40-4

4

45-4

9

50-5

4

55-5

9

60-6

4

65-6

9

70-7

4

75-7

9

80-8

4

≥85

1

Inci

denc

e pe

r 1

00

,00

0

Inci

denc

e pe

r 1

00

,00

0

Age group (months)

Age (years)

0

5

10

15

4-5 6-11 12-15 16-19 20-23≤3

MaleFemale

6

EPIDEMIOLOGY OF MENINGOCOCCAL DISEASE

prospective surveillance study of U.S. college students

with meningococcal infection during the 1998–1999

school year, serogroup C was the most common (48% of

isolates for which serogroup data were available), followed

by B, Y and W-135 (28%, 19% and 1%, respectively).23

The cyclic nature of disease and

changing distribution of serogroups,

combined with frequency of travel

worldwide, underscore the need

for a prevention strategy that

incorporates all major serogroups.

N. meningitidis is an aerobic, gram-negative

diplococcus. The bacterium has an outer membrane

that is surrounded by a protective polysaccharide

capsule. Thirteen antigenically and chemically

unique polysaccharide capsules have been identified

and form the basis of serogroup classification of

the organism. Five serogroups — A, B, C, Y and

W-135 — cause nearly all cases of invasive

meningococcal disease.

Figure 2:Serogroup Distribution of Invasive Meningococcal Disease by Age Group in the U.S. – Active Bacterial Core Surveillance 2002

Source: ABCs2

0

10

20

30

40

50

60

70

80

90

100

≤1 2-4 5-17 18-34 35-49 50-64 ≥65

Per

cent

of

Cas

es

B Other Y C

Age (years)

7

transmission of N. MENINGITIDIS occurs by droplet aero-

solization (e.g., coughing or sneezing) or direct contact

with secretions from the nasopharynx of colonized persons.

Whether the organism remains a colonizer of the

nasopharynx or crosses the mucosal barrier and gains

access to the bloodstream, central nervous system and/or

other organs depends on both specific bacterial virulence

factors (e.g., fimbriae, polysaccharide capsule, IgA

protease) and host defense mechanisms (e.g., mucosal

epithelium, secretory IgA, serum antibody, ciliary activity,

complement, blood-brain barrier).24

Various medical conditions increase the risk of

developing meningococcal disease. Persons with immature

or dysfunctional humoral immunity are most susceptible

to meningococcal infection.25,26 Immune defects that

predispose to meningococcal disease include functional

or anatomical asplenia, deficiency of properdin and

mannose-lectin binding protein and terminal complement

components.27-29 Antecedent respiratory tract infection

also has been associated with increased risk of

meningococcal disease.30,31 Finally, evidence indicates

genetic risk factors may increase susceptibility to

meningococcal infection.32,33

Likewise, certain environmental factors have been

shown to increase the risk of meningococcal disease.

The infection rate (secondary infection) is 500- to

800-fold greater in household contacts exposed to a

person who has a sporadic meningococcal infection

than in the general population.34 Increased risk of

meningococcal infection among military recruits35 and

college freshmen living in dormitories23 is likely a

consequence of crowded living conditions.

In the U.S., higher rates of meningococcal disease have

been observed in black persons and persons of low

socio-economic status, which are likely surrogate risk

markers (e.g., for household crowding and exposure to

tobacco smoke) rather than inherent genetic risk factors

for disease.36 Active smoking and passive exposure to

tobacco smoke increase the risk of illness, most likely by

increasing the creation and dissemination of respiratory

droplets or compromising the respiratory mucosa as a

barrier to microbial invasion.37 During outbreaks, bar or

nightclub attendance and alcohol consumption have

been identified as risk factors for infection.38-40

Once N. meningitidis enters the nasopharynx, the organism

attaches to and multiplies on nonciliated epithelial cells.

Some exposed individuals become asymptomatic

nasopharyngeal carriers of N. meningitidis,13,14 which is

an immunizing event. In less than 1% of colonized persons,

N. meningitidis penetrates the nasopharyngeal mucosa and

causes a systemic infection.17 In the bloodstream, the

organism can rapidly produce and release endotoxin,

which stimulates cytokine production and the alternative

complement pathway.7 In about half of bacteremic

persons, N. meningitidis crosses the blood-brain barrier

into the cerebrospinal fluid (CSF), and meningitis follows.

TRANSMISSION AND PATHOGENESIS: EXAMINING RISK FACTORS

Increased risk of meningococcal

infection among military recruits

and college freshmen living in

dormitories is likely a consequence

of crowded living conditions.

8

The quadrivalent meningococcal conjugate vaccine

(MCV4, Menactra®) is recommended for routine vaccination

(Table 1) of young adolescents at the pre-adolescent

health care visit (11-12 years of age).1 For those persons

who have not previously received MCV4, vaccination is

recommended before high-school entry (approximately

15 years of age). Also, if not previously vaccinated, routine

vaccination is recommended for college freshmen living in

dormitories. Finally, other adolescents and college students

who wish to decrease their risk for meningococcal disease

may elect to receive the vaccine.

The ACIP recommends catch-up vaccination at approxi-

mately 15 years of age as an effective strategy to reduce

meningococcal disease incidence among adolescents and

young adults. The routine vaccination recommendation

at 11-12 years of age might strengthen the role of the

pre-adolescent visit and have a positive effect on vaccine

coverage among adolescents. A routine visit at 11-12 years

of age to assess immunization status and other preventive

services is recommended by the ACIP, American Academy

of Pediatrics (AAP), American Academy of Family Physicians

(AAFP) and the American Medical Association (AMA).41

Routine meningococcal vaccination is also recommended

for persons in specific risk groups.1 These are microbiolo-

gists routinely exposed to isolates of N. meningitidis;

military recruits; persons who travel to, or reside in

countries in which N. meningitidis is hyperendemic or

epidemic; persons with terminal complement component

deficiencies; and those who have anatomic or functional

asplenia. HIV patients who wish to decrease their risk of

meningococcal disease may elect to be vaccinated.

Conjugate Versus Polysaccharide VaccineVaccination with MCV4 is preferred for all persons in

the age range for which it is approved, 11 to 55 years,

because of the benefits it should provide compared with

polysaccharide vaccine (Table 2).1 Immunogenicity data

show MCV4 induces antibody levels at least as good as the

polysaccharide vaccine. Both vaccines include protection

against four of the five strains (A, C, Y and W-135) that

cause the majority of cases worldwide. Neither includes

protection against serogroup B disease (see box, “About

Serogroup B Vaccines”).

Although the vaccines are equally immunogenic,

MCV4, which is administered intramuscularly (versus

subcutaneous injection of the polysaccharide vaccine) is

more reactogenic.1 MCV4 is expected to have a duration

of protection of at least 8 years compared with 3 to 5

years for the polysaccharide vaccine. Ongoing studies will

provide specific data about duration of protection in the

coming years.

U.S. IMMUNIZATION RECOMMENDATIONS

Table 1:Recommendations for Use of Meningococcal Conjugate Vaccine*

• At the pre-adolescent health care visit (11-12 years old)

• At high-school entry (approximately 15 years old), if not previously vaccinated with MCV4

• College freshmen living in dormitories

• Microbiologists routinely exposed to isolates of N. meningitidis

• Military recruits

• International travelers and citizens residing in endemic or hyperendemic areas

• Persons with anatomic or functional asplenia

• Persons with terminal complement component disorders

* Approved for use in persons aged 11 to 55 years Source: CDC1

9

In fact, extensive post-licensure evaluation of MCV4 will

be ongoing. Data collected in the coming years will pro-

vide vaccine-specific information and will shape future

recommendations. The hope is that this conjugate vaccine

provides benefits similar to other conjugate vaccines.

Conjugate technology changes the nature of the immune

response from T-cell independent to T-cell dependent. This

leads to benefits not seen with polysaccharide vaccines,

including induction of immunologic memory, booster

responses and reduction in nasopharyngeal bacterial

carriage. Reduction in asymptomatic carriage rates, if wide-

spread, leads to protection of unvaccinated individuals

through a herd immunity effect. These benefits have been

demonstrated with use of a monovalent meningococcal

conjugate C vaccine in the U.K. and widespread Hib and

pneumococcal conjugate vaccination in the U.S. (discussed

below). Data on similar benefits are not yet available on MCV4.

Table 2:Comparison: Conjugate and Polysaccharide Meningococcal Disease Vaccines

Conjugate (Menactra®) Polysaccharide (Menomune®)

Strains included A, C, Y, W-135 A, C, Y, W-135

Immunogenicity* 82% to 97% 80% to 95%

Duration of protection > 8 years† 3-5 years

Administration Intramuscular injection Subcutaneous injection

Safety Generally mild adverse reactions; mainly pain, redness and induration at injection site, headache, fatigue and malaise.

Generally mild adverse reactions; most frequent is pain and redness at injection site. Severe reaction uncommon.

Induction of immunologic memory‡ Expected No

Booster responses‡ Expected No

Reduction in nasopharyngeal bacterial carriage‡

Expected No

Herd immunity‡ Expected under some vaccination strategies No

Cost§ $82 $86

* Measured as ≥four-fold rises in antibody titers in adolescents; † Based on CDC model, ongoing evaluation is expected to provide direct data in three to five years; ‡ Assumptions based on demonstrated benefits of other conjugate vaccines § Retail cost to physicians.

Sources: CDC1, CDC unpublished data.

About Serogroup B Vaccines

In clinical trials, most candidate vaccines against

serogroup B polysaccharide have not stimulated

protective immunity in humans.42 Research has

focused on noncapsular antigens as vaccine

candidates. For example, an outer-membrane

protein serogroup B vaccine, licensed for use in

New Zealand in 2004, was designed to match

and combat an outbreak of serogroup B disease

ongoing throughout the 1990s. However, this

approach does not address the diversity of outer-

membrane proteins that cause sporadic serogroup

B disease or geographic variations.43,44

10

The quadrivalent meningococcal polysaccharide vaccine

(Menomune®, sanofi pasteur) continues to be recom-

mended in children aged 2 to 10 years and adults older

than 55 years who are at increased risk of infection. The

polysaccharide vaccine is also an acceptable alternative for

persons aged 11 to 55 years if MCV4 is unavailable.

Both vaccines are recommended for control of menin-

gococcal disease outbreaks, with the conjugate vaccine

preferred for those aged 11 to 55 years. Revaccination may

be indicated for those who previously received the poly-

saccharide vaccine if they remain at high risk for infection

and are aged 11 to 55 years.

Benefits of Other Conjugate VaccinesNon-meningococcal conjugate vaccines, including Hib

and a 7-valent pneumococcal, are routinely used in the

U.S. Before introduction of the vaccine, Hib disease was

the leading cause of bacterial meningitis in children

younger than 5 years. Incidence of invasive Hib disease

has declined more than 99% since vaccine licensure.45

Similarly, rates of invasive pneumococcal disease

in children younger than 2 years have declined 70% to

80% since vaccine licensure in 2000.2,12 Conjugate

pneumococcal vaccination also appears to have a

substantial herd immunity effect. While the vaccine is

used only in children, disease rates have declined among

adults. For the serotypes included in the vaccine, disease

incidence decreased in those aged 20 to 39 years, 40 to

64 years and 65 years and older by 46%, 20% and 29%,

respectively (CDC. Unpublished data).

The U.K. Experience: Monovalent Meningococcal Conjugate C VaccineAdditional evidence comes from the U.K., where a

comprehensive monovalent meningococcal conjugate C

vaccine immunization program was implemented in 1999.9

Disease epidemiology in the U.K. differs from that in the

U.S.; the U.K. sees very little serogroup Y disease and has

a higher incidence of serogroup C infection. Widespread

use of the monovalent conjugate C vaccine would be

expected to have a greater relative impact in the U.K.

The U.K. program includes a routine 3-dose infant

vaccination course (at 2, 3 and 4 months) with a single

dose for children aged 12 months to 17 years (with a

subsequent extension to 25 years of age).9 Immunization

rates of about 85% in target groups resulted in an 81%

reduction in serogroup C disease incidence within 18

months. While the vaccine was immunogenic in young

infants, their immunity waned at about 1 year.46

Despite this, control of disease in all age groups has been

excellent with disease incidence declining 67% in the

unvaccinated population.10 This is attributable to the herd

immunity arising from the marked reduction in nasopha-

ryngeal carriage (a key feature of conjugate vaccines).

Nasopharyngeal carriage rates decreased 66% among

students aged 15 to 17 years.47 Surveillance has shown

no evidence of serogroup replacement or development

of capsular switching in the first 18 months in the U.K.48

MCV4 will be used much differently in the U.S. than the

monovalent vaccine is used in the U.K. It is unclear if the

current U.S. immunization strategy will yield a herd

immunity benefit.

11

Meningitis and MeningococcemiaMeningococcal disease

manifests most commonly

as meningitis and/or menin-

gococcal bacteremia.7,8 It is

meningococcemia, however,

a less common but more

severe presentation (5% to 20% of cases) that is associated

with the highest mortality rates and long-term sequelae.

Meningococcemia often begins with a sudden onset of

fever, malaise, myalgia and headache; seizures occur in

20% of cases. About half of patients49 (even more chil-

dren and young adults)50 develop a prominent petechial

or purpuric rash, primarily on the extremities. When

present, a meningococcal rash can change and spread

very rapidly. Meningococcemia may occur either with

or without meningitis.

The more common clinical presentation, meningococcal

meningitis, is often nonspecific. Early symptoms may mimic

those of other more common but less serious diseases.5,8

Patients may present with sudden onset of fever, headache,

meningismus and signs of cerebral dysfunction. However,

the classic triad of headache, confusion and nuchal rigidity

is not always evident. Wide variations in presentation can

occur at all ages, and symptoms can progress and change

rapidly during the course of the disease.

Infants and the elderly may not present with the classic

symptoms and signs of meningococcal meningitis.51

Meningismus is absent in neonates and often in infants.52

One of the most important clues to a meningitis diagnosis

in neonates is a change in affect or level of alertness.

Clinical suspicion should also be raised by temperature

instability, listlessness, high-pitched crying, lethargy, weak

suck, refusal to eat, irritability, jaundice, vomiting, diarrhea

PRESENTATIONS, PROGRESSION AND SEQUELAE

CASE REVIEW: 12-year-old male

A 12-year-old African-American boy was rushed to the

emergency room by his parents at 5 p.m. on a Saturday

after they found him unresponsive in the bathroom.

Otherwise healthy, he had had two days of a non-productive

cough accompanied by malaise, headache and intermittent

nausea. He had been seen that morning by his physician

who prescribed azithromycin for bronchitis. It had taken

some time to fill the prescription and the boy received only

one dose of the medication, which he promptly vomited just

before he was discovered in the bathroom.

In the emergency department, the boy had no detectable

blood pressure and required immediate intubation. A few

petechial lesions were evident on the palms and soles

of the feet, at the belt line and in the conjunctivae. The

peripheral white blood cell count was 25,900/cumm with

a profound left shift and a platelet count of 35,500/cumm.

Antimicrobials and pressor agents were started immediately.

A lumbar puncture revealed a white cell count of 19,340

with 85% neutrophils and a glucose concentration of 16

mg/dl. Both blood and CSF culture grew N. meningitidis.

The patient had a prolonged, stormy course. He never

regained consciousness, developed purpura fulminans and

peripheral gangrene that required bilateral below-the-knee

amputation. He died of pulmonary complications after 33

days in the hospital.

Teaching Points: Symptoms of meningococcemia can

appear suddenly and progress rapidly. Even with rapid

diagnosis and appropriate treatment, serious sequelae are

possible; deafness being the most common one in children.

Meningococcal rashes may appear at areas where pressure

occurs from stockings, elastic or belts.

12

or respiratory distress. Elderly patients, especially those

with multiple co-morbid diseases, may be afebrile or

hypothermic, lethargic or exhibit reduced alertness and

have variable signs of meningeal inflammation. Confusion

is common,53 as is a prior or concurrent respiratory tract

infection. A definitive diagnosis of meningococcal disease

is based on isolation of N. meningitidis from a normally

sterile site (e.g., blood; CSF; joint, pleural or pericardial fluid).

Meningococcal meningitis is fatal in approximately 10%

of cases among the general population; the case fatality

rate is as high as 53% in patients with meningococcemia.7

Factors associated with an increased mortality rate include

recovery of an isolate from the bloodstream and serogroup

C infection.6

Other Presentations Up to 15% of patients with meningococcal disease have

pneumonia.6,54,55 Meningococcal pneumonia occurs

primarily in older adults and is most commonly associated

with serogroup Y or W-135 infection.6 Less common mani-

festations of disease (<2% of cases) include pericarditis,

otitis media, epiglottitis and arthritis (Figure 3).6

SequelaeEven with appropriate therapy, systemic meningococcal

infection can progress rapidly — often within hours of the

first symptoms. Despite the susceptibility of N. meningitidis

to penicillin and advances in medical care, 11% to 19% of

patients who survive invasive meningococcal disease suffer

from permanent sequelae, including hearing loss, neurologic

or brain damage, renal failure and limb amputation.7,8

Prevention of Secondary DiseaseThe primary method of preventing secondary meningo-

coccal disease is antimicrobial prophylaxis of persons in

close contact with an infected person (Table 3). Those

Figure 3:Clinical Manifestations of Meningococcal Disease

PRESENTATIONS, PROGRESSION AND SEQUELAE

Source: Rosenstein6

Table 3:Meningococcal Disease Prophylaxis Recommendations: High-Risk Contacts

• Household contact (especially young children)

• Child care or nursery school contact*

• Direct exposure to secretions of index patient through kissing, sharing toothbrushes or eating utensils (markers of close social contact)*

• Mouth-to-mouth resuscitation, unprotected contact during endotracheal intubation*

• Frequently slept or ate in same dwelling as index patient*

* During 7 days before onset of illnessSource: AAP60

Pneumonia 6.0%

Bacteremia 43.3%

Arthritis 2.0%

Epiglottitis 0.3%

Pericarditis 0.1%

Otitis media 1.0%

Meningitis 47.3%

13

most in need of chemoprophylaxis against meningococcal

infection include household members, daycare center

contacts and persons directly exposed to the oral

secretions of a patient with invasive meningococcal

infection. Antimicrobial prophylaxis of at-risk persons

should be initiated within 24 hours after the index

infection is identified, if possible.11

Oral rifampin and ciprofloxacin and parenteral ceftriaxone

substantially reduce (by 90% to 95%) nasopharyngeal

carriage of N. meningitidis56-59 and are therefore

recommended by the ACIP and the AAP for prophylaxis of

meningococcal disease (Table 4).11,60 One study showed

azithromycin is also effective in eradicating nasopharyngeal

carriage.61 Persons with invasive meningococcal disease

treated with agents other than ceftriaxone or other third-

generation cephalosporins should also receive one of the

chemoprophylactic antibiotics before hospital discharge.62

Outbreak ControlGiven the devastating nature of meningococcal disease,

sporadic cases often become the topic of front-page and

TV news. Such cases elicit community fear and increased

telephone calls and visits to treatment centers. Public

An 18-year-old white female attending a state univer-

sity (freshman dormitory resident) began to experience

aches and chills while at class during the third week of

the semester. The patient assumed she had a mild viral

illness and returned to the dorm to sleep. Shortly after

dinner, she went to the infirmary complaining of aches

and nausea. The patient reported that she came to the

infirmary at the urging of her roommate. The patient was

articulate and mildly febrile (101ºF); she expressed a

desire to go back to her room. Infirmary staff agreed and

ordered Tylenol and rest.

In the morning, when she did not join her friends at

breakfast, they went to the patient’s room to check on

her. She was in bed, and friends described her as “inco-

herent” and “confused.” The friends brought the patient

back to the infirmary where staff noticed a rash on her

torso. Transport to a local hospital took approximately 35

minutes.

Antibiotics were started within 15 minutes of arrival in the

emergency department. The white blood cell count was

12,500/cumm with a marked left shift. Although the blood

culture was negative, the CSF culture was positive for

N. meningitidis, Group C. The patient was hospitalized

for 8 days and was discharged to the care of her parents

at home. She re-started her college studies during the

second semester. Subsequent testing determined that the

patient had sustained a moderate high and mid-range

bilateral hearing loss.

Teaching Points: Early symptoms of meningococcal

infection can mimic other mild to generally moderate

illnesses (e.g., cold and flu). The onset of symptoms in

this patient was insidious and, upon her first presentation

to the infirmary, non-specific. The cognitive dysfunction

was not evident until her second visit to the infirmary.

Meningococcal disease was not immediately evident

(e.g., she had no rash or high fever) upon her initial pre-

sentation in the university infirmary. Therapy should be

started upon suspicion of meningococcal infection and

not withheld pending results of cultures.

CASE REVIEW: 18-year-old female

14

health departments are faced with assessing potential

outbreaks, determining the need for and designing

appropriate control procedures and fielding public

inquiries. Requests for chemoprophylaxis and vaccination

are common, even among those without close contact

with infected persons.

The decision to implement mass vaccination is

complicated.11 Such vaccination campaigns are expensive,

require considerable public health effort and can create

unwarranted public concern. Still, mass vaccination may

be necessary to prevent the substantial morbidity and

mortality associated with meningococcal disease. The

CDC has issued guidelines, including criteria for deciding

whether use of meningococcal vaccine is warranted

(available at: www.cdc.gov/mmwr/pdf/rr/rr4605.pdf).

Economic Impact and Cost EffectivenessAn economic cost and benefit analysis of routine menin-

gococcal vaccination at 11 years of age showed that costs

associated with this intervention are high compared with

many other recommended preventive measures.63 A similar

analysis examining routine vaccination in college freshmen

also highlighted the high cost of a widespread meningo-

coccal vaccination program.64 Both analyses included a

wide range of costs associated with each meningococcal

disease case. The high end of these ranges demonstrates

the potential for serious disease sequelae and even death

that accompany each infection.

Although data about the economic impact of meningococcal

disease are imperfect, older CDC data estimated the direct

cost of meningococcal disease at $13,431 per case (1995

dollars).65 The estimated lifetime costs of sequelae ranged

from $44,187 per case (hearing loss) to $864,980 (severe

retardation). Indirect costs (lost productivity) were estimated

to be $1 million per case. Preventing disease would avert

these costs for the individual, families, health care providers,

employers, health care payers and society.

Drug Age Group Dosage and Route of Administration Duration

Ciprofloxacin Adults 500 mg po Single dose

Ceftriaxone Children < 15 yrsAdults

125 mg IM250 mg IM

Single doseSingle dose

Rifampin Children < 1 moChildren > 1 moAdults

5 mg/kg po q12h10 mg/kg po q12h600 mg po q12h

2 days2 days2 days

Table 4:Schedule for Antibiotic Prophylaxis of Meningococcal Disease

Sources: CDC1, AAP60

15

CONCLUSION

meningococcal disease is a serious illness that can

progress rapidly, resulting in substantial morbidity

and mortality, even with appropriate treatment. U.S.

immunization policy shifted with the availability of

a quadrivalent conjugate meningococcal vaccine.

The conjugate vaccine is approved for use in persons

aged 11 to 55 years and recommended for routine

vaccination of adolescents and college freshmen living

in dormitories. Others at high risk and therefore

recommended for vaccination include microbiologists

routinely exposed to isolates of N. meningitidis,

international travelers or U.S. citizens living in areas where

N. meningitidis is endemic or hyperendemic, those with

anatomic or functional asplenia or terminal complement

component disorders and military recruits.

The constantly changing epidemiology, coupled with

the ease and frequency of travel of U.S. citizens, suggests

broad coverage against meningococcal serogroups is

warranted. Although no vaccine against serogroup B is

available currently, the quadrivalent meningococcal

conjugate and polysaccharide vaccines both provide pro-

tection against the other four clinically relevant strains

of N. meningitidis (A, C, Y, W-135). The conjugate vaccine

is available for persons aged 11 to 55 years while the

polysaccharide vaccine is approved for use in anyone

aged 2 years or older and recommended for those aged

2 to 10 and 55 years and older.

Health care providers must also be aware of the variable

and potentially fulminant clinical presentation of menin-

gococcal disease. The difficulty of a quick and accurate

diagnosis and the occurrence of substantial morbidity

and mortality even with appropriate and rapid treatment

are compelling reasons for a conjugate vaccine-based

approach to the prevention of meningococcal disease.

16

REFERENCES

1. Centers for Disease Control and Prevention. Prevention and control of meningococcal disease: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2005;54(RR-7):1-21.

2. Active Bacterial Core Surveillance (ABCs) 1997-2001 meningococcal surveillance reports. Available at: www.cdc.gov/ncidod/dbmd/abcs/. Accessed July 15, 2004.

3. Centers for Disease Control and Prevention. Prevention and con-trol of meningococcal disease and meningococcal disease and college students — recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2000; 49(RR-7):1-22.

4. Harrison LH, Pass MA, Mendelsohn AB, et al. Invasive meningococcal disease in adolescents and young adults. JAMA 2001; 286:694-699.

5. Apicella MA. Neisseria Meningitidis. In: Mandel GL, Bennett JE, Dolin R., eds, Principles and Practice of Infectious Diseases. 5th ed. Philadelphia, PA: Churchill Livingstone; 2000:2228-2241.

6. Rosenstein NE, Perkins BA, Stephens DS, et al. The changing epidemiology of meningococcal disease in the United States, 1992-1996. J Infect Dis 1999; 180:1984-1901.

7. Kirsch EA, Barton P, Kitchen L, Giroir BP. Pathophysiology, treatment, and outcome of meningococcemia: A review and recent experience. Pediatr Infect Dis J 1996; 15:967-979.

8. Edwards MS, Baker CJ. Complications and sequelae of meningococcal infections in children. J Pediatr 1981; 99:540-545.

9. Miller E, Salisbury D, Ramsay M. Planning, registration, and implementation of an immunisation campaign against meningococcal serogroup C disease in the UK: A success story. Vaccine 2002; 20(suppl 1):S58-S67.

10. Ramsay ME, Andrews NJ, Trotter CL, Kaczmarski EB, Miller E. Herd immunity from meningococcal serogroup C conjugate vaccine in England: Database analysis. BMJ 2003; 326:365-366.

11. Centers for Disease Control and Prevention. Control and prevention of meningococcal disease and control and prevention of serogroup C meningococcal disease: Evaluation and management of suspected outbreaks —recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1997; 46(RR-5):1-21.

12. Whitney CG, Farley MM, Hadler J, et al, for the Active Bacterial Core Surveillance of the Emerging Infections Program Network. Decline in invasive pneumococcal disease after the introduction of protein-polysaccharide conjugate vaccine. N Engl J Med 2003; 348:1737-1746.

13. Greenfield S, Sheehe PR, Feldman HA. Meningococcal carriage in a population of “normal” families. J Infect Dis 1971; 123:67-73.

14. Caugant DA, Hoiby EA, Magnus P, et al. Asymptomatic carriage of Neisseria meningitidis in a randomly sampled population. J Clin Microbiol 1994; 32:323-330.

15. Cartwright KA, Stuart JM, Jones DM, Noah ND. The Stonehouse survey: Nasopharyngeal carriage of meningococci and Neisseria lactamica. Epidemiol Infect 1987; 99:591-601.

16. Stephens DS. Uncloaking the meningococcus: Dynamics of carriage and disease. Lancet 1999; 353:941-942.

17. Aycock WL, Mueller JH. Meningococcus carrier rates and meningitis incidence. Bacteriol Rev 1950; 14:115-160.

18. Centers for Disease Control and Prevention. Notice to readers: Risk for meningococcal disease associated with the Hajj 2001. MMWR 2001;50(6):97-98.

19. Schwartz B, Moore PS, Broome CV. Global epidemiology of meningococcal disease. Clin Microbiol Rev 1989; 2(suppl):S118-S124.

20. Riedo FX, Plikaytis BD, Broome CV. Epidemiology and prevention of meningococcal disease. Pediatr Infect Dis J 1995; 14:643-657.

21. Rosenstein NE, Perkins BA, Stephens DS, Popovic T, Hughes JM. Meningococcal disease. N Engl J Med 2001; 344:1378-1388.

22. Parent du Chatelet I, Traore Y, Gessner BD, et al. Bacterial meningitis in Burkina Faso: surveillance using field-based polymerase chain reaction testing. Clin Infect Dis. 2005;40(1):17-25.

23. Bruce MG, Rosenstein NE, Capparella JM, et al. Risk factors for meningococcal disease in college students. JAMA 2001; 286:688-693.

24. Tunkel AR, Scheld WM. Pathogenesis and pathophysiology of bacterial meningitis. Clin Microbiol Rev 1993; 6:118-136.

25. Goldschneider I, Gotschlich EC, Artenstein MS. Human immunity to the meningococcus: I. The role of humoral antibodies. J Exp Med 1969; 129:1307-1326.

26. Goldschneider I, Gotschlich EC, Artenstein MS. Human immunity to the meningococcus: II. Development of natural immunity. J Exp Med 1969; 129:1327-1348.

27. Figueroa JE, Densen P. Infectious diseases associated with complement deficiencies. Clin Microbiol Rev 1991; 4:359-395.

28. Franke EL, Neu HC. Postsplenectomy infection. Surg Clin N Am 1981; 61:135-155.

29. Van Dueren M, Brandtzaeg P, van der Meer JW. Update on meningococcal disease with emphasis on pathogenesis and clinical management. Clin Microbiol Rev 2000; 13:144-156.

30. Cartwright KA, Jones DM, Smith AJ, Stuart JM, Kaczmarski ER, Plamer SR. Influenza A infection and meningococcal disease. Lancet 1991; 338:554-557.

31. Moore PS, Hierholzer J, DeWitt W, et al. Respiratory viruses and mycoplasma as cofactors for epidemic group A meningococcal meningitis. JAMA 1990; 264:1271-1275.

32. Hibberd ML, Sumiya M, Summerfield JA, Booy R, Levin M. Association of variant of the gene mannose-binding lectin with susceptibility to meningococcal disease. Lancet 1999; 353:1049-1053.

33. Nadel S, Newport MJ, Booy R, Levin M. Variation in the tumor necrosis factor-alpha gene promotor region may be associated with death from meningococcal disease. J Infect Dis 1996; 174:878-880.

17

34. Meningococcal Disease Surveillance Group. Analysis of endemic meningococcal disease by serogroup and evaluation of chemoprophylaxis. J Infect Dis 1976; 134:201-204.

35. Brundage JF, Ryan MA, Feighner BH, Erdtmann FJ. Meningococcal disease among United States military service members in relation to routine uses of vaccines with different serogroup-specific components, 1964-1998. Clin Infect Dis 2002;35(11):1376-1381.

36. Jackson LA, Wenger JD. Laboratory-based surveillance for meningococcal disease in selected areas, United States, 1989-1991. MMWR 1993; 42(SS-2):21-30.

37. Fischer M, Hedberg K, Cardosi P, et al. Tobacco smoke as a risk factor for meningococcal disease. Pediatr Infect Dis J 1997; 16:979-983.

38. Imrey PB, Jackson LA, Ludwinski PH, et al. Meningococcal carriage, alcohol consumption, and campus bar patronage in a serogroup C meningococcal disease outbreak. J Clin Microbiol 1995; 33:3133-3137.

39. Imrey PB, Jackson LA, Ludwinski PH, et al. Outbreak of serogroup C meningococcal disease associated with campus bar patronage. Am J Epidemiol 1996; 143:624-630.

40. Cookson ST, Corrales JL, Lotero JO, et al. Disco fever: Epidemic meningococcal disease in Northeastern Argentina associated with disco patronage. J Infect Dis 1998; 178:266-269.

41. Centers for Disease Control and Prevention. Immunization of Adolescents — Recommendations of the Advisory Committee on Immunization Practices, the American Academy of Pediatrics, the American Academy of Family Physicians, and the American Medical Association. MMWR 1996;45(RR-13):1-17.

42. Soriano-Gabarró M, Stuart JM, Rosenstein NE. Vaccines for the prevention of meningococcal disease in children. Semin Pediatr Infect Dis 2002;13:182-189.

43. Tondella MLC, Popovic T, Rosenstein NE, et al. Distribution of Neisseria meningitidis serogroup B sero-subtypes and serotypes circulating in the United States. J Clin Microbiol 2000;38:3323-3328.

44. Sacchi CT, Whitney AM, Popovic T, et al. Diversity and prevalence of PorA types in Neisseria meningitidis serogroup B in the United States, 1992-1998. J Infect Dis 2000;182:1169-1176.

45. Centers for Disease Control and Prevention. Progress toward elimination of Haemophilus influenzae type b invasive disease among infants and children — United States, 1998-2000. MMWR 2002;51(11):234-237.

46. Trotter CL, Andrews NJ, Kaczmarski EB, Miller E, Ramsay ME. Effectiveness of meningococcal serogroup C conju-gate vaccine 4 years after introduction. Lancet 2004; 364:365-367.

47. Maiden MCJ, Stuart M, for the UK Meningococcal Carriage Group. Carriage of serogroup C meningococci 1 year after meningococcal C conjugate polysaccharide vaccine. Lancet 2002; 359:1829-1830.

48. Balmer P, Borrow R, Miller E. Impact of meningococcal serogroup C conjugate vaccine 4 years after introduction. Lancet 2004;364:717-722.

49. Roos KL, Tunkel AR, Scheld WM. Acute bacterial meningitis in children and adults. In: Scheld WM, Whitley RJ, Durack DT, eds. Infections of the Central Nervous System. 2nd ed. Philadelphia, PA: Lippincott-Raven;1997:335-401.

50. Anderson J, Backer V, Voldsgaard P, et al. Acute meningococcal meningitis: Analysis of features of the disease according to the age of 255 patients. J Infect 1997; 34:227-235.

51. Tunkel AR, Scheld WM. Acute meningitis. In: Mandel GL, Bennett JE, Dolin R, eds, Principles and Practice of Infectious Diseases. 5th ed. Philadelphia, PA: Churchill Livingstone; 2000:959-997.

52. Saez-Llorens X, McCracken GH Jr. Bacterial meningitis in neo-nates and children. Infect Dis Clin North Am 1990; 4:623-644.

53. Gorse GJ, Thrupp LD, Nudleman KL, et al. Bacterial meningitis in the elderly. Arch Intern Med 1989; 149:1603-1606.

54. Racoosin JA, Whitney CG, Conover C, Diaz PS. Serogroup Y meningococcal disease in Chicago, 1991-1997. JAMA 1998; 280:2094-2098.

55. Griffiss JM, Yamasaki R, Eastbrook M, Kim JJ. Meningococcal molecular mimicry and the search for an ideal vaccine. Trans R Soc Trop Med Hyg 1991; 85 (suppl 1):S32-S36.

56. Broome CV. The carrier state: Neisseria meningitidis. J Antimicrob Chemother 1986;18 (suppl A):25-34.

57. Gaunt PN, Lambert SE. Single dose ciprofloxacin for the eradication of pharyngeal carriage of Neisseria meningitidis. J Antimicrob Chemother 1988; 21:489-496.

58. Dworzack DL, Sanders CC, Horowitz EA, et al. Evaluation of single-dose ciprofloxacin in the eradication of Neisseria meningitidis from nasopharyngeal carriers. Antimicrob Agents Chemother 1988; 32:1740-1741.

59. Schwartz B, Al-Tobaiqi A, Al-Ruwais A, et al. Comparative efficacy of ceftriaxone and rifampin in eradicating pharyngeal carriage of group A Neisseria meningitidis. Lancet 1988; 2:1239-1242.

60. American Academy of Pediatrics. Meningococcal infections. In: Pickering LK, ed. Red Book: 2003 Report of the Committee on Infectious Diseases. 26th ed. Elk Grove, IL: American Academy of Pediatrics; 2003.

61. Girgis N, Sultan Y, Frenck RW Jr, El-Gendy A, Farid Z, Mateczun A. Azithromycin compared with rifampin for eradication of nasopharyngeal colonization by Neisseria meningitidis. Pediatr Infect Dis J 1998;17:816-819.

62. Abramson JS, Spika JS. Persistence of Neisseria meningitidis in the upper respiratory tract after intravenous antibiotic therapy of systemic meningococcal disease. J Infect Dis 1985; 151:370-371.

63. Shepard CW, Ortega-Sanchez I, Corso P, Scott RD, Rosenstein N, ABCs team. Cost-effectiveness of conjugate meningococcal vaccination strategies in the United States. In: Abstracts of the 42nd Annual Meeting of the Infectious Diseases Society of America, Boston, Massachusetts, September 30-October 3, 2004: p.60.

64. Scott RD, Meltzer MI, Erickson LJ, De Wals P, Rosenstein N. Vaccinating first-year college students living in dormitories for meningococcal disease, an economic analysis. Am J Prev Med 2002;23:98-105.

65. Levine OS, Shaffer P, Haddix A, Perkins BA. Cost-effectiveness analysis for routine immunization with a quadrivalent meningococcal polysaccharide (A, C, Y, W-135) protein conjugate vaccine in the United States. Presented at the Tenth International Pathogenic Neisseria Conference, Baltimore, MD, September 1996.

18

1. What percent of meningococcal disease cases in the

U.S. are fatal?

a) <4

b) 4 to 6

c) 6 to 10

d) 10 to 14

2. What percent of meningococcal disease survivors

experience permanent sequelae (e.g., hearing loss,

brain damage, renal failure or limb amputation)?

a) 4 to 7

b) 8 to 10

c) 11 to 19

d) ≥20

3. What is the most common cause of bacterial

meningitis in the U.S.?

a) Haemophilus influenzae type b

b) Neisseria meningitidis

c) Staphylococcus aureus

d) Streptococcus pneumoniae

4. Which serogroup, commonly responsible for U.S.

epidemics a century ago, now rarely causes infection

in this country?

a) A

b) C

c) Y

d) W-135

5. Which serogroup caused 2% of cases in the early

1990s, but nearly 40% by the end of the decade?

a) A

b) C

c) Y

d) W-135

6. Which factors affect whether N. meningitidis crosses

the mucosal barrier and gains access to the

bloodstream, CNS and other organs?

a) Bacterial virulence

b) Host defense mechanisms

c) Neither A nor B

d) Both A and B

7. Which symptom is absent in neonates with

meningococcal meningitis?

a) Change in affect or alertness level

b) Fever

c) Headache

d) Meningismus

8. Incidence of invasive Hib disease has fallen by what

percent following widespread uptake of the conjugate

Hib vaccine?

a) 50

b) 70

c) 90

d) >99

9. Which benefit is not associated with use of the

polysaccharide meningococcal vaccine?

a) Highly effective in older children and adults

b) Favorable safety profile

c) Lifelong immunity

d) Protection against serogroups A, C, Y and W-135

10. Conjugate vaccines are associated with which

benefit(s) versus polysaccharide vaccines?

a) Herd effect

b) Improved duration of activity

c) Induction of immunologic memory

d) All of the above

SELF-ASSESSMENT EXAMINATIONPlease circle the correct answer. (At least seven of the ten answers must be correct to obtain a CME certificate.) See mailing instructions on next page.

19

Your input is extremely important and valuable to us. Please take the time to complete the following evaluation giving us your assessment of this CME activity.

1. This content meets the educational objectives

a) agree

b) neutral

c) disagree

2. Considering my experience, the material

presented was

a) satisfactory

b) too elementary

c) too technical

3. I gained information which will be useful to me

a) agree

b) neutral

c) disagree

4. The format is clear, readable and useful

a) agree

b) neutral

c) disagree

5. There was commercial bias in this activity

a) yes

b) no

If yes, please give examples:

________________________________________________

________________________________________________

________________________________________________

________________________________________________

Suggested topics for future issues or other comments

about this publication:

________________________________________________

________________________________________________

________________________________________________

________________________________________________

CME EVALUATION

Name ____________________________________________ Degree: ___________________________________________

Title: ____________________________________________ Organization: ______________________________________

Street Address: ____________________________________ E-mail Address: _____________________________________

City: _____________________________________________ State: _______________ Zip Code: _____________________

Signature: _______________________________________________________________ Date: _________________________

Instructions for obtaining CME creditsTo receive CME credits after reading the publication, complete the self-assessment examination, the CME evaluation, and your contact information. Return the examination and evaluation form, including your complete contact information, via fax to 301-907-0878 or by mail to:

NFID Office of CME4722 Bethesda Avenue, Suite 750Bethesda, Maryland 20814

No fee is required. Please allow 4-6 weeks for processing your certification. Inquiries may be directed by phone to 301-656-0003 ext. 19 or by e-mail to info@nfid.org. Requests for credit must be received no later than November 2007.

(Please print legibly or we will be unable to process your certificate.)

National Foundation for Infectious Diseases

4733 Bethesda Avenue, Suite 750

Bethesda, Maryland 20814